The overall goal of the application is to define the role of products of a cytochrome P450 w-hydroxylase enzyme located in cerebral arterial muscle in mediating pressure-induced activation and hypoxia-induced inhibition of the cerebral vasculature. They will test the hypothesis that autoregulation of cerebral blood flow and the cerebral vascular response to hypoxia are mediated by a common mechanism involving regulation of smooth muscle potassium channel activity and membrane potential. They plan to test the ability of the cerebral vasculature to form the P450 w-hydroxylase product 20-HETE upon elevation of transmural and arterial pressure, and the ability of reduced PO2 to inhibit such production. They also plan to determine if the action of hypoxia, and the parenchymal/endothelial factors released by hypoxia involves increasing potassium channel activity and hyperpolarizing the vascular muscle membrane. They will also determine if there is linkage between increased P450 w-hydroxylase activity in response to increasing transmural pressure and the cerebral vascular responses to changes in PO2.